中文摘要：

白质消融性白质脑病（Ieukoencephalopathy with vanishing whitematter，VWM，OMIM#603896）是儿童期起病的最常见遗传性白质脑病之一，其特殊性在于此病是迄今为止已知的唯一由于真核细胞蛋白质翻译启动异常所导致的人类遗传病。对此病发病机制的深入研究将为进一步了解蛋白质翻译启动这一重要而复杂的生理过程以及蛋白质翻译异常性疾病的共同发生机制提供重要线索。

英文摘要：

SUMMARY Leukoencephalopathy with vanishing white matter （VWM） is one of the most prevalent inherited white matter disorders in childhood, and it＇s the only known hereditary human disease due to the direct defects in protein synthesis process, with the gene defects in EIF2B1 -5, encoding the five subunits of eukaryotic translation initiation factor （eIF2B α, β, γ, δ and ε） respectively, eIF2B is essential for the protein translation initiation process, and its action is realized via eukaryotic translation initiation factor2 （eIF2）. Phosphorylation of eIF2α and eIF2Bε is an important way to regulate eIF2B function, and thus play a key role in control of the protein translation level under physiological condition. Mutant eIF2B results in functional defects and decrease of the overall protein translation in cells, but in increase the translation of proteins with multiple upstream open reading frames, such as activating transcription factor 4 （AFF4）, which leads to the susceptibility to un-folded protein response under stress, and the following apoptosis. The exact pathogenic mechanisms of VWM are far from well understood. It＇s suggested that level of AFT4 in cells with eIF2B mutations is higher than in wild type cells under physiological condition, which makes the mutant cells more susceptible to endoplasmic reticulum （ER） stress and unfolded protein response （UPR）. Under stress, the defect elF2B leads to a vicious cycle of UPR activation, which may underlie the neurological aggravation in VWM patients after minor stress, a specific clinical feature of VWM. Elucidating the pathogenesis of VWM will be helpful to further understand the protein translation process in eukaryotic cells, and provide a clue for possible therapeutic targets and treatment strategies in the future.